In the past, it has been known to use swallowable electronic capsules to collect data and transmit the data to a receiver system. Such capsules are generally known as “Heidelberg” capsules and have been used in the intestines to measure things such as pH, temperature and pressure. Other in vivo measuring systems that have been used are endoscopes, which are long tubes that a patient swallows. Endoscopes are often used to provide images of the upper or lower gastrointestinal tract, but since they typically are not very flexible and are not moved easily through small intestines, conventional endoscopes do not provide views of the small intestines. Also, endoscopes are uncomfortable, may injure a patient, and are complex to operate. Fiber-optic endoscopes utilize a fiber-optic waveguide to transmit a video signal from an area of interest to the electronics located outside of a patient's body. Video endoscopes place an electronic camera at an area of interest and transmit and store the images until after the test finishes.
Early detection of pre-malignant lesions, such as adenomatous polyps, and malignant lesions is crucial in the prevention and early treatment of common gastrointestinal cancers. With the advent of fiberoptic endoscopes such as EGD and colonoscopy whose flexibility allows an endoscopist to traverse the duodenum and the colon, lesions within the reach of the endoscope can now be detected, albeit invasively. Major portions of the small intestine, however, remain inaccessible by the conventional endoscope. In addition, fiberoptic endoscopy also has a small but significant risk of bleeding, perforation and sedation-associated cardiopulmonary incident.
Video capsule endoscopy is a minimally invasive procedure that involves swallowable camera capsules that can be used for imaging the gastrointestinal tract. Images from the video capsule can be wirelessly transmitted from the capsule to an electronic receiver outside of the body. An early example of such a video capsule is disclosed in U.S. Pat. No. 5,604,531. Such video capsules typically use white light for guidance and imaging within the gastrointestinal tract. Using conventional video capsules, however, the images generated can only indicate the presence of something, for example on an interior wall along the gastrointestinal tract. The ability to determine information such as, for example, the clinical classification of polyps such as benign (hyperplastic and lymphoid) versus pre-malignant (adenomatous) is extremely limited. Conventional video capsule endoscopy does not provide the possibility of tissue sampling, and only anatomic and morphologic information can be extracted from white light imaging.
Molecular imaging utilizing probes activated by biomarkers associated with neoplastic lesions is emerging as a powerful tool to detect and distinguish pre-malignant and malignant lesions. Such imaging involves certain molecular biomarkers such as some proteases being up-regulated in neoplastic lesions. Probes activated by these biomarkers, termed “molecular beacons”, are becoming increasingly valuable tools for detecting cancerous lesions and differentiating benign and pre-malignant polyps. This new technology, utilizes special near infrared fluorescent (NIRF) imaging probes carrying non-fluorescent enzyme substrates. These are essentially undetectable after systemic administration unless locally activated by enzymes associated with disease processes. Such probes are typically injected intravenously and in vivo detection of specific enzyme activity is achieved through imaging hardware capable of detecting near-infrared light emissions. One such NIRF imaging probe used currently only in experimental animal models is based on Cathepsin B, a proteolytic enzyme that is consistently overexpressed in adenomatous polyps and cancers. In mouse models these probes have been used on dissected gastrointestinal tissue and on anesthetized mice with modified fiberoptic endoscopy. The latter application still involves invasive endoscopic methods and if applied clinically would have limitations similar to conventional endoscopy.
Accordingly, in light of the current technologies for video capsule endoscopy, significant room for improvement in the art remains for improved capsule imaging devices, systems and methods for non-invasive or less invasive in vivo imaging applications, such as for gastrointestinal applications. Improved capsule imaging devices that can distinguish and differentiate pre-malignant and malignant lesions, inflammatory lesions, and which can differentiate lesions at regions of the gastrointestinal tract not accessible by conventional endoscopic techniques are exemplary of desirable improvements.